Phosphonic acid catalyst in dehydrative cyclization of 5 and 6 carbon polyols with improved color and product accountability

ABSTRACT

A process for preparing cyclic dehydration products from sugar alcohols is described. The process involve using a mixed-acid catalyst reaction mixture containing a reducing acid, having a pKa of about 1.0-1.5, and at least a strong Brønsted acid or a Lewis acid, having a pKa≦0, or both acids in a solution to dehydrate and ring close said sugar alcohol. Synergistically, the mixed-acid catalysis can produce greater amounts of the desired product at similar levels of compositional accountability than either of the component acid catalysts acting alone.

BENEFIT OF PRIORITY

The present application claims benefit of priority from InternationalApplication Nos. PCT/US2014/033580, and PCT/US2014/033581, both filedApr. 10, 2014, and International Application No. PCT/US2014/66298, filedNov. 19, 2014, the contents of each are incorporated herein byreference.

FIELD OF INVENTION

The present invention relates to certain bi-functional molecules andtheir preparation. In particular, the present invention pertains to acatalytic dehydration process of sugar alcohols to generatedianhydro-sugars.

BACKGROUND

Traditionally, polymers and commodity chemicals have been prepared frompetroleum-derived feedstocks. However, as petroleum reservoirs arerapidly depleting and concomitantly becoming more difficult to access,an exigency to develop renewable or “green” alternative materials frombiologically-derived resources has been at the vanguard of much currentresearch, particularly in the role of commercially tenable surrogates toconventional, petroleum-based or -derived counterparts, or forgenerating the same materials as produced from fossil, non-renewablesources.

One of the most abundant kinds of biologically-derived or renewablealternative feedstock for such materials is carbohydrates.Carbohydrates, however, are generally unsuited to current hightemperature industrial processes. In contrast to petroleum-based,hydrophobic aliphatic or aromatic feedstocks with a low degree offunctionalization, carbohydrates such as sugars are complex, highlyfunctionalized hydrophilic materials. As a consequence, researchers havesought to produce biologically-based chemicals that originate fromcarbohydrates, but which are less highly functionalized, including morestable bi-functional compounds, such as 2,5-furandicarboxylic acid(FDCA), levulinic acid, and 1,4:3,6-dianhydrohexitols.

1,4:3,6-dianhydrohexitols (also referred to herein as isohexides) arederived from renewable resources from cereal-based polysaccharides.Isohexides embody a class of bicyclic furanodiols that derive from thecorresponding reduced sugar alcohols, namely D-sorbitol, D-mannitol, andD-iditol, respectively. Depending on chirality, the three isomers of theisohexides are: A) isosorbide, B) isomannide, and C) isoidide,respectively, the structures of which are illustrated in Scheme 1.

The conventional chemistry used for dehydration of sugar alcohols toproduce dianhydrohexides generates undesired byproducts. The high costand complexity of current methods for the separation of isohexides fromthe numerous byproducts makes the development of less expensive andsimpler alternatives highly desirable. Hence, a process which canenhance greater conversion and higher yield of the desired product, aswell as lessens amount of byproducts would be welcome.

SUMMARY OF THE INVENTION

The present disclosure describes, in part, a process for preparing acyclic dehydration product. The process involves contacting a sugaralcohol with a mixed-acid catalyst reaction mixture containing areducing Brønsted acid, having a pKa of about 1.0-1.5, in combinationwith at least a strong Brønsted acid or a Lewis acid, having a pKa<0, orboth kinds of strong Brønsted and Lewis acids in a solution at atemperature and for a time sufficient to dehydrate and ring close thesugar alcohol molecule to a corresponding cyclic dehydration product ina product mixture. The process can enable marked improvements in overallconversion rates and product yields, without significant deleteriouseffects on the level of product accountability, and reduced color bodyformation.

The ratio of reducing acid and at least a Brønsted acid or Lewis acidare present in relative amounts from about 1000:1 to about 5:1. Theprocess can produce at least a 3% increase in relative yield of adianhydro-sugar product relative to a dehydration reaction using eitherthe reducing Brønsted acid, the strong Brønsted acid, or Lewis acidseparately and alone under the same respective acid catalyst load forthe same reaction time and temperature.

Additional features and advantages of the present processes will bedisclosed in the following detailed description. It is understood thatboth the foregoing summary and the following detailed description andexamples are merely representative of the invention, and are intended toprovide an overview for understanding the invention as claimed.

BRIEF DESCRIPTION OF FIGURES

FIG. 1 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 10 mol. % H₃PO₃, alone, 2) 0.1 mol. % H₂SO₄, alone,and 3) combining the two in a mixed acid catalyst, at 140° C. for 2 h.(120 min.).

FIG. 2 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 10 mol. % H₃PO₃, alone; 2) 0.1 mol. % H₂SO₄, alone;and 3) combining the two in a mixed acid catalyst, at 150° C. for 1 h.(60 min.).

FIG. 3 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 5 mol. % H₃PO₃, alone, 2) 0.1 mol. % H₂SO₄, alone, and3) combining the two in a mixed acid catalyst, at 140° C. for 2 h. (120min.).

FIG. 4 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 5 mol. % H₃PO₃, alone, 2) 0.1 mol. % H₂SO₄, alone, and3) combining the two in a mixed acid catalyst, at 150° C. for 1 h. (60min.).

FIG. 5 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 10 mol. % H₃PO₃, alone, 2) 0.1 mol. % p-TsOH, alone,and 3) combining the two in a mixed acid catalyst, at 140° C. for 2 h.(120 min.).

FIG. 6 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 10 mol. % H₃PO₃, alone, 2) 0.1 mol. % p-TsOH, alone,and 3) combining the two in a mixed acid catalyst, at 150° C. for 1 h.(60 min.).

FIG. 7 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 5 mol. % H₃PO₃, alone, 2) 0.1 mol. % p-TsOH, alone,and 3) combining the two in a mixed acid catalyst, at 140° C. for 2 h.(120 min.).

FIG. 8 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 5 mol. % H₃PO₃, alone, 2) 0.1 mol. % p-TsOH, alone,and 3) combining the two in a mixed acid catalyst, at 150° C. for 1 h.(60 min.).

FIG. 9 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 2.5 mol. % H₃PO₃, alone, 2) 0.1 mol. % p-TsOH, alone,and 3) combining the two in a mixed acid catalyst, at 140° C. for 2 h.(120 min.).

FIG. 10 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 2.5 mol. % H₃PO₃, alone, 2) 0.1 mol. % p-TsOH, alone,and 3) combining the two in a mixed acid catalyst, at 150° C. for 1 h.(60 min.).

FIG. 11 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 5 mol. % H₃PO₃, alone, 2) 0.005 mol. % Ga(OTf)₃,alone, and 3) combining the two in a mixed acid catalyst, at 140° C. for2 h. (120 min.).

FIG. 12 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 5 mol. % H₃PO₃, alone, 2) 0.005 mol. % Ga(OTf)₃,alone, and 3) combining the two in a mixed acid catalyst, at 130° C. for3 h. (180 min.).

FIG. 13 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 5 mol. % H₃PO₃, alone, 2) 0.01 mol. % Ga(OTf)₃, alone,and 3) combining the two in a mixed acid catalyst, at 110° C. for 1 h.(60 min.).

FIG. 14 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 5 mol. % H₃PO₃, alone, 2) 0.01 mol. % Ga(OTf)₃, alone,and 3) combining the two in a mixed acid catalyst, at 140° C. for 2 h.(120 min.).

FIG. 15 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 5 mol. % H₃PO₃, alone, 2) 0.01 mol. % Ga(OTf)₃, alone,and 3) combining the two in a mixed acid catalyst, at 130° C. for 3 h.(180 min.).

FIG. 16 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 5 mol. % H₃PO₃, alone, 2) 0.05 mol. % Ga(OTf)₃, alone,and 3) combining the two in a mixed acid catalyst, at 140° C. for 2 h.(120 min.).

FIG. 17 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 5 mol. % H₃PO₃, alone, 2) 0.05 mol. % Ga(OTf)₃, alone,and 3) combining the two in a mixed acid catalyst, at 150° C. for 1 h.(60 min.).

FIG. 18 is a bar graph showing the compositional accountability of theproduct mixture from three dehydration cyclization reactions of sorbitolcatalyzed with 1) 5 mol. % H₃PO₃, alone, 2) 0.1 mol. % Ga(OTf)₃, alone,and 3) combining the two in a mixed acid catalyst, at 150° C. for 1 h.(60 min.).

FIG. 19 is a bar graph showing the relative composition and percentaccountability of product mixtures for dehydrative cyclization ofsorbitol using three different catalysts in combination and each alone:5 mol. % H₃PO₃, 0.01 mol. % Bi(OTf)₃, and 0.05 mol. % p-TsOH, 150° C., 1h. (60 min.).

FIG. 20 is a bar graph showing the relative composition and percentaccountability of product mixtures for dehydrative cyclization ofsorbitol using three different catalysts in combination and each alone:2.5 mol. % H₃PO₃, 0.01 mol. % Bi(OTf)₃, and 0.1 mol. % p-TsOH, 150° C.,1 h. (60 min.).

FIG. 21 is a bar graph showing the relative composition and presentaccountability of product mixtures for dehydrative cyclization ofsorbitol using three different catalysts in combination and each alone:5 mol. % H₃PO₃, 0.01 mol. % Hf(OTf)₄, and 0.05 mol. % p-TsOH, 150° C., 1h. (60 min.).

FIG. 22 is a bar graph showing the relative composition and percentaccountability of product mixtures for dehydrative cyclization ofsorbitol using a combination of 10 mol. % H₃PO₃, and 0.1 mol. % H₂SO₄co-catalysis, at different temperatures (170° C. & 190° C.) and forvarious time periods.

FIG. 23 is a bar graph showing for purposes of comparison the relativecomposition and percent accountability of product mixtures fordehydrative cyclization of sorbitol using only sulfuric acid catalyst atdifferent catalyst load, temperature, and reaction times.

DETAILED DESCRIPTION OF THE INVENTION

The present disclosure describes a process that can improve conversionand yields, and enhance compositional accountability in product mixturesprepared from dehydration reactions of sugar alcohols. In general, theprocess involves contacting a sugar alcohol with a mixed-acid catalystcontaining a reducing Brønsted acid, having a pKa of about 1.0-1.5, andeither a strong Brønsted acid or Lewis acid, having a pKa≦0, or bothacids in a solution to dehydrate and ring close the sugar alcoholmolecule to its corresponding cyclic dehydration product.

When a sugar alcohol is dehydrated by an acid catalyst some byproductsare typically formed. These undesired products and are not easilyidentifiable, meaning there are products formed that are not identifiedas a particular cyclic dehydration derivative species (e.g., anisohexide or sorbitan compound). These difficult to identify byproductsinclude polymeric condensates and color bodies, both of which impart anunwanted color and opacity to the reaction mixture. “Accountability” asused herein, is a measure of the percentage of the product mixture thatcan be quantitatively identified as cyclic dehydration derivativecompounds and unreacted starting materials, but excludespoly-condensates, color bodies or other species (e.g., furaniccompounds) that are not identified as a cyclic dehydration product.

The methods described herein are exemplified by use of phosphonic acid(H₃PO₃) also known as phosphorus acid as the reducing Brønsted acid, toperform the dehydration of sugar alcohols to their corresponding cyclicderivatives. According to an advantageous feature of the presentmethods, use of phosphonic acid in combination with other acids todehydrate sugar alcohols results in a product mixture with highaccountability relative to a dehydration reaction catalyzed with asingle acid (e.g., sulfuric acid).

We discovered surprisingly that a combination of two or more acidcatalysts has significant synergistic benefits as reflected inconversion yields of cyclic dehydration products (e.g., dianhydrosugarcompounds) and compositional accountability results. In general, themixed-acid catalysis can produce greater amounts of desired product atcomparable levels of compositional accountability than either of thecomponent acid catalysts acting alone. According to the process, thereaction leads to a product mixture having at least a 3%-5% increase inrelative yield of a specific cyclic dehydration product relative to adehydration reaction using either the reducing Brønsted acid, the strongBrønsted acid, or Lewis acid separately and alone under the samerespective acid catalyst loads for the same reaction time andtemperature. In certain embodiments, the relative yield of specificcyclic dehydration products relative to a dehydration reaction catalyzedwith each of the acids singly or separately is increased by about 7% toabout 20% or greater (e.g., about 10% or 11% to about 15% or 18% withoptimization of reaction conditions). In certain favored embodiments,the yield from combined or multiple acid catalysis can be at leastdouble or triple the amount yielded from catalysis using the individualsingle acids in the combined catalysis.

In the product mixtures of the combined acid catalysis one does notobserve a significant build-up of color bodies, as attended by theproduct accountability, relative to the product mixtures from singleacid catalysis (see e.g., Table 2.). The reaction can generate a productmixture that has a relative percentage of compositional accountabilitythat is either a) equal to, b) greater than or c) not less than about20% (typically, not less than 12% to about 18%) of a compositionalaccountability derived from a dehydration reaction using either thereducing acid, the strong Brønsted acid, or Lewis acid separately andalone. In certain embodiments, the product accountability of thesynergistic combined acid catalysis is not less than about 2%-10%relative to that of a compositional accountability derived from adehydration reaction using either the reducing acid, the strong Brønstedacid, or Lewis acid separately and alone under the same respective acidcatalyst loads for the same reaction time and temperature. Toillustrate, the compositional accountability value for each of thecombined mixed-acid catalysis reactions in FIGS. 1 and 2 (respectively83.6% and 82.8%) is about equal to the accountability value for each ofthe reactions catalyzed with sulfuric acid alone (respectively 83.3% and82.6%), while also being slightly less than the value for each of thereaction using phosphonic acid alone (respectively 88.5% and 89.2%).Further, the compositional accountability value for each of the combinedmixed-acid catalysis reactions in FIGS. 11 and 12 (respectively 94.0%and 95.1%) is greater than the accountability value for each of thereactions catalyzed by phosphonic acid alone (respectively 89.7% and91.5%), while also being less than the accountability value for each ofthe reactions catalyzed by gallium triflate alone (respectively 99.9%and 100%).

The multiple or combined acid catalysis can be employed in theconversion of various different sugar alcohol species to theircorresponding products. According to certain embodiments, the sugaralcohol can be, for example, sorbitol, mannitol, iditol, xylitol anderythritol. Alternatively, the reagent can be a dehydration product ofsugar alcohols, such as 1,2,5,6-hexanetetrol (HTO). For instance,sorbitol is converted to isosorbide by means of intramoleculardehydrative cyclization of sorbitol to sorbitans, then isosorbide. Inanother example, xylitol can be dehydrated directly to1,4-anhydroxylitol. Alternatively, HTO is cyclized dehydratively toracemic THF dimethanols.

The reducing Brønsted acid may be at a catalyst load of about 0.5 mol. %or 1 mol. % or 2 mol. % to about 15 mol. % or 20 mol. %, relative to theconcentration of the sugar alcohol, or any combination of range valuestherein. In certain other embodiments, the phosphonic acid is at acatalyst load in a range from about 5 mol. % or 7 mol. % to about 10mol. % or 13 mol. % In favored embodiments, the reducing Brønsted acidis phosphonic acid (H₃PO₃).

The strong Brønsted acid can be, for example, hydrochloric acid (HCI),sulfuric acid (H₂SO₄), p-toluenesulfonic acid (p-TsOH), methane sulfonicacid, or trifluoromethansulfonic acid.

The Lewis acid is water tolerant. That is, the Lewis acid is notdeactivated in the presence of water. The Lewis acid may include atleast one of: aluminum trifluoromethanesulfonate (Al(OTf)₃), galliumtrifluoromethanesulfonate (Ga(OTf)₃, bismuth trifluormethanesulfonate(Bi (OTf)₃), scandium trifluoromethanesulfonate (Sc(OTf)₃), indiumtrifluoromethanesulfonate (In(OTf)₃), tin triflate (Sn(OTf)₂), andhafnium triflate (Hf(OTf)₄).

The strong Brønsted acid or Lewis acid each may have a catalyst load ofabout 0.005 mol. % or 0.1 mol. % to about 2 mol. % or about 5 mol. %,relative to the concentration of the sugar alcohol. In general, theamount of reducing Brønsted acid present is greater than either strongBrønsted acid or Lewis acid catalyst loadings. The amount of reducingBrønsted acid catalyst and either strong Brønsted acid or Lewis acidcatalyst allotted in the combined acid catalysis is in a ratio fromabout 1000:1 to about 5:1, inclusive of various combination rangestherein between. Ideally, given the highly reactive nature of Lewisacids, the reducing Brønsted acid vs. Lewis acid loading is about 100:1to 1000:1. Typically, the ratios can be about 250:1, 200:1, 150:1, or100:1. For the present disclosure, the Lewis acid activity in descendingorder is: Hf>Ga>Sc>Bi>In>Al>Sn. Ideally, the reducing Brønsted acid vs.strong Brønsted acid loading is about 100:1 to 5:1. Typically, theratios can be narrower, about 70:1, 50:1, 40:1 to about 20:1, 15:1, or10:1.

The reaction time can be about 4 or 6 hours, but typically to minimizecolor body formation the reaction times are shorter, between about 1hour to about 2.5 or 3 hours. (See e.g., Table 2.)

The reaction temperature may be in a range from about 100° C. up toabout 180° C. or 190° C. Typically, the reaction temperature is in arange from about 110° C. to about 150° C. or 165° C.

To obtain optimal product yields, the dehydration reaction is performedunder vacuum at an operating pressure of about 5 torr to about 100 ton.Typically, the operating pressure is between about 10 ton to about 30torr, preferably between about 12 or 15 ton to about 20 or 25 ton.

1. Sugar Alcohol

While the advantageous features of the processes described herein areexemplified with sorbitol dehydration, the present processes can beemployed for transforming various sugar alcohol or dehydration productcompounds of sugar alcohols (e.g., sorbitol, mannitol, iditol, xylitol,erythritol, and 1,2,5,6-hexanetetrol (HTO)) in the preparation of theirdehydration products.

For purpose of illustration, Table 1 summarizes the results of catalyticdehydration reactions of sorbitol under various reaction conditionsaccording to embodiments of the present process. In Examples 1-21, thedehydration reactions use phosphonic acid (H₃PO₃), at several differentcatalyst loads that range from about 2.5 mol. % to about 10 mol. % incombination with some examples of strong Brønsted and Lewis acids, alsoat various catalyst loads. These reactions are performed at varioustemperatures between about 110° C. to about 150° C., over a period ofabout 1, 2, or 3 hours. As the results show, several examples of thephosphonic acid catalysis can produce relatively good rates ofconversion of sorbitol to isosorbide without significant loss ofcomposition accountability levels for the product mixture. The yield ofisosorbide is either better than or comparable to reactions that use astrong Brønsted acid, such as sulfuric acid (H₂SO₄) as the catalyst.(See, Comparative Examples 1-7 in Table 3.) In certain examples, thecombination of phosphonic acid catalyst with a strong, water-tolerantLewis acid catalyst, such as bismuth triflate (Bi(OTf)₃), generatesimproved yields of isosorbide relative to the use of the Lewis acidalone.

Phosphonic acid exhibits an inherently reductive ability and antioxidantbehavior. It is believed that the phosphonic acid functions both as acatalyst for dehydrative cyclization and as reducing agent to helpmitigate color development in the product. From the examples and resultsin the accompanying figures, a favored range for operating conditions ofthe dehydrative reactions may include phosphonic acid with aconcentration of about 2 mol % or 5 mol % to about 10 mol % or 20 mol %,depending on the reaction time and temperature. Longer durations andhigher temperatures should be balanced for optimal reaction results.

The unique utility and significant performance characteristics ofphosphonic acid as a catalyst can generate both good conversion ratesand product accountabilities. Certain examples with differentcombinations of catalyst loads, temperature, and time exhibitedparticularly advantageous results. This suggests potential improvementsin combined acid systems. The higher isosorbide yield in the sampleshighlight a beneficial impact of phosphonic acid with strong Brønstedand Lewis acids, in particular when present at higher acidconcentrations.

In Example 1-4, the sulfuric acid catalysis of sorbitol yields about20-24 wt. % of isosorbide, with about 80%-84% product accountability.The phosphonic acid catalysis of sorbitol produces about 5-20 wt. % ofisosorbide, with about 85-85% product accountability. The combined acidcatalysis generally produces about 1.3-2× greater amount of isosorbide(e.g., ˜25-45 wt. %) than the dehydrative reactions using each of thesingle acid catalysts alone, with comparable levels of productaccountability (e.g., ˜80-87%).

These results compare favorably to similar results for the reactions inExamples 5-10, which present catalysis with p-toluenesulfonic acid,phosphonic acid, and combination of the two acids. Sorbitol catalyzedwith p-TsOH alone yields about 5-9% of isosorbide, with about 89%-95%product accountability. The phosphonic acid catalysis of sorbitolproduces about 2-18% of isosorbide, with about 85-98% productaccountability. The combined acid catalysis generally produces about2-6× greater amount of isosorbide (e.g., ˜13-36 wt. %) than thedehydrative reactions using each of the single acid catalysts alone,with comparable levels of product accountability (e.g., ˜80% or 82% to94% or 95%).

Similarly, Examples 11-17 presents catalysis with galliumtrifluoromethanesulfonate, phosphonic acid, and combination of the twoacids. Sorbitol catalyzed with Ga(OTf)₃ alone yields minimal amounts ofisosorbide (0-1 wt. %), with about 89%-95% product accountability. Thephosphonic acid catalysis of sorbitol produces about 2-18% ofisosorbide, with about 85-98% product accountability. The combined acidcatalysis generally produces at least 2× or 3× greater amount ofisosorbide (e.g., ˜7-34 wt. %) than the dehydrative reactions using eachof the single acid catalysts alone, with comparable levels of productaccountability (e.g., ˜80% or 82% to 94% or 95%).

Given the highly reactive nature of the Lewis acid, the amount of Lewisacid employed is kept at a low concentration, which results in lowerconversion yields of isosorbide. In comparison, a change in the amountof acid used, as in Example 18, causes an increase in the reactivity byan order of magnitude to generate more isosorbide. In Example 18,sorbitol is catalyzed with a) aluminum trifluoromethanesulfonate, b)phosphonic acid, and a combination of the two acids (a & b) toisosorbide with yields of about 13.39 wt. %, 5.18 wt. %, and 40.07 wt.%, respectively. The product accountability is 89.0% for Al(OTf)₃, 94.1%for H₃PO₃, and 85.8% for the combined acids.

Examples 19 and 20 present catalysis using: bismuthtrifluoromethanesulfonate, p-toluenesulfonic acid, phosphonic acid, andcombination of the three component acids. Sorbitol catalyzed withBi(OTf)₃ alone yields minimal amounts of isosorbide (0-1 wt. %), withabout 97%-99% product accountability. The p-TsOH catalysis of sorbitolproduces about 2-8 wt. % of isosorbide, with about 90-95% productaccountability. The phosphonic acid catalysis of sorbitol produces about2-6% of isosorbide, with about 93-96% product accountability. Thecombined multi-acid catalysis generally produces at least 2× or 4×greater amount of isosorbide (e.g., ˜17-42 wt. %) than the dehydrativereactions using each of the single acid catalysts alone, with comparablelevels of product accountability (e.g., ˜85%-90%).

Example 21 summarizes catalysis using: hafniumtrifluoromethanesulfonate, p-toluenesulfonic acid, phosphonic acid, andmixed combination of the three component acids. Sorbitol catalyzed withHf(OTf)₄ alone yields about 6.62 wt. % of isosorbide, with about 96.6%product accountability. The p-TsOH catalysis of sorbitol produces about2.36 wt. % of isosorbide, with about 93.7% product accountability. Thephosphonic acid catalysis of sorbitol produces about 5.18% ofisosorbide, with about 94.1% product accountability. The combinedmulti-acid catalysis produces at least about 3× or 5× up to about 12×greater amount of isosorbide (e.g., ˜29.18 wt. %) than the dehydrativereactions using each of the single acid catalysts alone, with comparablelevels of product accountability (e.g., ˜86.3%).

TABLE 1 Summary of Co-catalysis Results Catalyst 1,4- 2,5-Accountability Accountability Load Time Temp Sorbitol Isosorbidesorbitan sorbitan(s) (%) w/o (%) + Ex. Catalysts (mol %) (min) (° C.)(wt. %) (wt. %) (wt. %) (wt. %) Catalyst Catalysts 1 H₃PO₃/H₂SO₄ 10/0.1 120 140 0 35.88 31.37 11.95 79.2 83.6 H₂SO₄ 0.1 120 140 0 21.74 49.2812.28 83.3 H₃PO₃ 10 120 140 0 12.30 55.24 16.88 88.5 2 H₃PO₃/H₂SO₄10/0.1  60 150 0 40.39 24.36 18.05 78.5 82.8 H₂SO₄ 0.1 60 150 0 23.8247.95 10.87 82.6 H₃PO₃ 10 60 150 0 16.33 57.50 15.37 89.2 3 H₃PO₃/H₂SO₄5/0.1 120 140 0 33.81 35.32 14.77 83.9 86.2 H₂SO₄ 0.1 120 140 0 21.7449.28 12.28 83.3 H₃PO₃ 5 120 140 20.8 9.76 52.10 7.05 89.7 4 H₃PO₃/H₂SO₄5/0.1 60 150 0 27.17 44.62 10.31 82.1 84.5 H₂SO₄ 0.1 60 150 0 23.8247.95 10.87 82.6 H₃PO₃ 5 60 150 24.47 5.18 49.00 15.40 94.1 5H₃PO₃/pTsOH 10/0.1  120 140 0 29.23 33.56 17.81 80.6 85.0 pTsOH 0.1 120140 17 6.92 63.22 6.26 93.4 H₃PO₃ 10 120 140 0 12.30 55.24 16.88 88.5 6H₃PO₃/pTsOH 10/0.1  60 150 0 32.43 32.11 15.96 80.5 84.9 pTsOH 0.1 60150 12.6 7.13 59.24 12.71 91.7 H₃PO₃ 10 60 150 0.0 16.33 57.50 15.3789.2 7 H₃PO₃/pTsOH 5/0.1 120 140 0 18.53 55.85 15.22 89.6 91.9 pTsOH 0.1120 140 17 6.92 63.22 6.26 93.4 H₃PO₃ 5 120 140 20.8 9.76 52.10 7.0589.7 8 H₃PO₃/pTsOH 5/0.1 60 150 0 14.12 53.51 16.37 84.0 87.0 pTsOH 0.160 150 13 7.13 59.24 12.31 91.7 H₃PO₃ 5 60 150 24.47 5.18 49.00 15.4094.1 9 H₃PO₃/pTsOH 2.5/0.1   120 140 0 20.19 50.64 9.49 87.5 89.2 pTsOH0.1 120 140 17 6.92 63.22 6.26 93.4 H₃PO₃ 2.5 120 140 43.5 2.23 40.2810.71 96.7 10 H₃PO₃/pTsOH 2.5/0.1   60 150 0 20.16 49.76 18.98 87.2 88.9pTsOH 0.1 60 150 13 7.13 59.24 12.31 91.7 H₃PO₃ 2.5 60 150 39.6 2.5141.68 11.62 95.4 11 H₃PO₃/Ga(OTf)₃  5/0.005 60 150 12.7 13.32 55.7514.03 95.8 Ga(OTf)₃ 0.005 60 150 82.18 0 14.69 3.17 100.0 H₃PO₃ 5 60 15024.47 5.18 49.00 15.40 94.1 12 H₃PO₃/Ga(OTf)₃  5/0.005 120 140 12.4611.62 55.92 14.04 94.0 Ga(OTf)₃ 0.005 120 140 78.5 0 25.16 3.77 99.9H₃PO₃ 5 120 140 20.8 9.76 52.10 7.05 89.7 13 H₃PO₃/Ga(OTf)₃  5/0.005 180130 21.1 7.22 52.88 13.90 95.1 Ga(OTf)₃ 0.005 180 130 89.2 0 10.62 1.92100.0 H₃PO₃ 5 180 130 33.2 2.91 42.61 12.81 91.5 14 H₃PO₃/Ga(OTf)₃ 5/0.01 60 150 4.2 15.09 58.44 14.49 89.8 92.2 Ga(OTf)₃ 0.01 60 150 67.00.63 24.79 5.99 98.4 H₃PO₃ 5 60 150 24.5 5.18 49.00 15.40 94.1 15H₃PO₃/Ga(OTf)₃  5/0.01 120 140 6.9 12.49 57.04 16.37 90.0 92.8 Ga(OTf)₃0.01 120 140 73.7 0.31 26.01 2.97 99.2 H₃PO₃ 5 120 140 20.8 9.76 52.107.05 89.7 16 H₃PO₃/Ga(OTf)₃  5/0.01 180 130 14.2 8.76 54.24 16.60 91.093.8 Ga(OTf)₃ 0.01 180 130 81.8 0.00 14.72 2.90 99.8 H₃PO₃ 5 180 13033.2 2.91 42.61 12.81 91.5 17 H₃PO₃/Ga(OTf)₃  5/0.05 120 140 0.0 24.1347.04 18.38 86.8 89.6 Ga(OTf)₃ 0.05 120 140 32.9 4.47 47.02 8.08 92.5H₃PO₃ 5 120 140 20.8 9.76 52.10 7.06 89.7 18 H₃PO₃/Ga(OTf)₃  5/0.05 60150 0.0 33.1 33.66 17.14 83.9 Ga(OTf)₃ 0.05 60 150 28.9 6.01 44.13 8.5387.6 H₃PO₃ 5 60 150 24.5 5.18 49.00 15.37 94.1 19 H₃PO₃/Al(OTf)₃ 5/0.160 150 0.0 40.07 27.76 17.98 85.8 Al(OTf)₃ 0.1 60 150 9.8 13.39 50.0215.77 89.0 H₃PO₃ 5 60 150 24.5 5.18 49.00 15.40 94.1 20 H₃PO₃/Bi(OTf)₃/5/0.01/0.05 60 150 0.0 19.63 48.96 18.52 87.1 pTsOH Bi(OTf)₃ 0.01 60 15074.6 0.00 19.42 4.38 98.4 p-TsOH 0.05 60 150 37.8 2.36 43.66 9.82 93.7H₃PO₃ 5 60 150 24.47 5.18 49.00 15.40 94.1 21 H₃PO₃/Bi(OTf)₃/2.5/0.01/0.1 60 150 0.0 39.07 29.01 20.45 88.5 p-TsOH Bi(OTf)₃ 0.01 60150 74.6 0.00 19.42 4.38 98.4 p-TsOH 0.1 60 150 13 7.13 59.24 12.31 91.7H₃PO₃ 2.5 60 150 39.6 2.51 41.68 11.62 95.4 22 H₃PO₃/Hf(OTf)₄/5/0.01/0.05 60 150 0.0 29.18 43.83 13.29 86.3 pTsOH Hf(OTf)₄ 0.01 60 15047.4 6.62 42.03 0.50 96.6 p-TsOH 0.05 60 150 37.8 2.36 43.66 9.82 93.7H₃PO₃ 5 60 150 24.47 5.18 49.00 15.40 94.1

Two sets of dehydrative cyclization reactions of sorbitol using a mixedacid catalyst of 10 mol. % H₃PO₃, and 0.1 mol. % H₂SO₄, at 170° C. and190° C., for various time periods were conducted. The relativecomposition and percent accountability of product mixtures for thereactions are summarized in Table 2, and presented graphically in FIG.22.

TABLE 2 Reaction time Temp. % molar yield % Sorbitol mol % mol % Sample# (min) (° C.) Sorbitans Isosorbide Sorbitol total*** Conversion H₃PO₃H₂SO₄ Color 1 48 170 30 1 67 98 33 10.0 0.1 pale yellow 2 60 169 44 2 55101 45 10.0 0.1 more gold 3 75 170 48 2 46 96 54 10.0 0.1 more gold 4 90170 64 4 36 104 64 10.0 0.1 more gold 5 final 95 170 66 5 35 105 65 10.00.1 more gold 6 30 190 70 5 38 113 62 10.0 0.1 golden from 7 60 190 76 829 112 71 10.0 0.1 start (5 min) 8 120 190 76 14 12 103 88 10.0 0.1 andnot much 9 final 125 190 84 22 4 111 96 10.0 0.1 color change

Product accountability was consistently high (>96%) even at the highertemperature. Color did not change dramatically in products obtained at190° C. from those when the reaction was performed at 170° C. In thepresent cases, the samples were gold color with no solid formation.Previously, the products of reactions catalyzed without the mixed acidcatalysts were generally dark in color and tar-like with high sorbitolconversion. (See for example, International Application No.PCT/US2014/66298, the contents of which are incorporated herein byreference.)

For purposed of comparison, Table 3 shows similar conversions can beobtained using sulfuric acid alone without H₃PO₃, in a concentratedsolution of sorbitol (˜65% DS). The ratio of sorbitans is higher in thepresence of H₃PO₃ at 170° C. and higher overall accountability at both170° C. and 190° C. The product mixture at 190° C. with sulfuric acid isdarker than that observed at 170° C. The process showed the processworks well with sulfuric acid at reasonable reaction times.

Reaction time Temp. % molar yield % mol % mol % Example (min) (° C.)Sorbitans Isosorbide Sorbitol conversion H₃PO₃ H₂SO₄ COLOR 1 10 170 38 264 36 0 2 bright yellow 2 15 170 40 2 52 48 0 2 bright yellow 3 20 17044 3 45 55 0 2 bright yellow 4 25 170 44 3 38 62 0 2 bright yellow 5 10185 80 11 14 86 0 2 amber 6 30 190 32 42 1 99 0.0 2.7 brown 7 10 190 5117 4 96 0.0 1.0 brown

2. Conversion Yield and Compositional Accountability

FIGS. 1-20, show in graphical form the data summarized in Table 1. Thefigures show the percentage of sorbitol converted to isosorbide andpercentage of product compositional accountability under variousreaction conditions (i.e., temperatures and times) using phosphonic acid(H₃PO₃) catalyst, at various catalyst loading levels, and a strongBrønsted acid and/or Lewis acid catalysts, at various catalyst loadinglevels, alone and in combination with the strong Brønsted acid and/orLewis acid catalysts.

In aggregate, the data suggests that one can control or modulate time,temperature, and catalyst load to balance and optimize desired targetyields and product accountability. The combined catalysts and highercatalyst loadings facilitate quick conversion of the sugar alcohol toits corresponding dehydration product at relatively low temperatures,with minimal reduction in product accountability.

In FIG. 1, sorbitol is converted to isosorbide using 10 mol. % H₃PO₃,0.1 mol. % H₂SO₄, 140° C., 2 h., in three reactions with each individualacid catalyst separately, and in combination. All of the sorbitol isconverted in all three reactions. The amount of isosorbide generated inthe phosphonic acid catalysis is about 12.30 wt. % of the reactionproduct mixture, the sulfuric acid catalysis is about 21.74 wt. % of thereaction product mixture, and in the combined phosphonic and sulfuricacid catalysis is about 35.88 wt. %. The combined acid catalysisgenerated more of isosorbide when compared to each of the single acidcatalysis, while also maintaining a comparable level of compositionalaccountability for the respective reaction product mixtures of the threeacid reactions. The product accountability of each of the reactions doesnot differ significantly from each other (i.e., 83.6% with H₃PO₃/H₂SO₄;83.3% with H₂SO₄; 88.5% with H₃PO₃).

In FIG. 2, again, sorbitol is converted to isosorbide using 10 mol. %H₃PO₃, 0.1 mol. % H₂SO₄, 150° C., 1 h., in three reactions with eachindividual acid catalyst separately, and in combination. Again, all ofthe sorbitol is converted in all three reactions. The amount ofisosorbide generated in the phosphonic acid catalysis is about 16.33 wt.% of the reaction product mixture, the sulfuric acid catalysis is about23.82 wt. % of the reaction product mixture, and in the combinedphosphonic and sulfuric acid catalysis is about 40.39 wt. %. Thecombined acid catalysis generated more of isosorbide when compared toeach of the single acid catalysis, while maintaining concomitantly acomparable level of compositional accountability for the respectivereaction product mixtures of the three acid reactions. The productaccountability of each of the reactions ranged from 82.8% withH₃PO₃/H₂SO₄; 82.6% with H₂SO₄; 89.2% with H₃PO₃.

In FIG. 3, sorbitol is converted to isosorbide using 5 mol. % H₃PO₃, 0.1mol. % H₂SO₄, 140° C., 2 h., in three reactions with each individualacid catalyst separately, and in combination. The amount of isosorbidegenerated in the phosphonic acid catalysis is about 9.76 wt. % of thereaction product mixture, the sulfuric acid catalysis is about 21.74 wt.% of the reaction product mixture, and in the combined phosphonic andsulfuric acid catalysis is about 33.81 wt. %. The combined acidcatalysis generated more of isosorbide when compared to each of thesingle acid catalysis, while maintaining concomitantly a comparablelevel of compositional accountability for the respective reactionproduct mixtures of the three acid reactions. The product accountabilityof each of the reactions ranged from 86.2% with H₃PO₃/H₂SO₄; 83.3% withH₂SO₄; 89.7% with H₃PO₃. All of the sorbitol is consumed in the combinedacid and H₂SO₄ catalysis, while a significant percent remains unreactedfor the H₃PO₃ (20.8%) single acid catalysis.

In FIG. 4, sorbitol is converted to isosorbide using 5 mol. % H₃PO₃, 0.1mol. % H₂SO₄, 150° C., 1 h., in three reactions with each individualacid catalyst separately, and in combination. The amount of isosorbidegenerated in the phosphonic acid catalysis is about 5.18 wt. % of thereaction product mixture, the sulfuric acid catalysis is about 23.82 wt.% of the reaction product mixture, and in the combined phosphonic andsulfuric acid catalysis is about 27.17 wt. %. The combined acidcatalysis generated more of isosorbide when compared to each of thesingle acid catalysis, while maintaining concomitantly a comparablelevel of compositional accountability for the respective reactionproduct mixtures of the three acid reactions. The product accountabilityof each of the reactions ranged from 84.5% with H₃PO₃/H₂SO₄; 82.6% withH₂SO₄; 94.1% with H₃PO₃. All of the sorbitol is consumed in the combinedacid and H₂SO₄ catalysis, while a significant percent remains unreactedfor the H₃PO₃ (24.47%) single acid catalysis.

In FIG. 5, sorbitol is converted to isosorbide using 10 mol. % H₃PO₃,0.1 mol. % p-TsOH, 140° C., 2 h., in three reactions with eachindividual acid catalyst separately, and in combination. The amount ofisosorbide generated in the phosphonic acid catalysis is about 12.30 wt.% of the reaction product mixture, the p-TsOH catalysis is about 6.92wt. % of the reaction product mixture, and in the combined p-TsOH andphosphonic acid catalysis is about 29.23 wt. %. The combined acidcatalysis generated about 2-3 times more isosorbide when compared to thesingle acid catalysis, while maintaining concomitantly a comparablelevel of compositional accountability for the respective reactionproduct mixtures of the three acid reactions. The product accountabilityof each of the reactions ranged from 85.0% with H₃PO₃/p-TsOH; 93.4% withp-TsOH; 88.5% with H₃PO₃. All of the sorbitol is consumed in thecombined acid and H₃PO₃ catalysis, while a significant percent remainsunreacted for the p-TsOH (17%) single acid catalysis.

In FIG. 6, sorbitol is converted to isosorbide using 10 mol. % H₃PO₃,0.1 mol. % p-TsOH, 150° C., 1 h., in three reactions with eachindividual acid catalyst separately and in combination. The amount ofisosorbide generated in the phosphonic acid catalysis is about 16.33 wt.% of the reaction product mixture, the p-TsOH catalysis is about 7.13wt. % of the reaction product mixture, and in the combined p-TsOH andphosphonic acid catalysis is about 32.43 wt. %. The combined acidcatalysis generated about 2-3 times more of isosorbide when compared tothe single acid catalysis, while maintaining concomitantly a comparablelevel of compositional accountability for the respective reactionproduct mixtures of the three acid reactions. The product accountabilityof each of the reactions ranged from 84.9% with H₃PO₃/p-TsOH; 91.7% withp-TsOH; 89.2% with H₃PO₃. All of the sorbitol is consumed in thecombined acid and H₃PO₃ catalysis, while a significant percent remainsunreacted for the p-TsOH (12.6%) single acid catalysis.

In FIG. 7, sorbitol is converted to isosorbide using 5 mol. % H₃PO₃, 0.1mol. % p-TsOH, 140° C., 2 h., in three reactions with each individualacid catalyst separately, and in combination. The amount of isosorbidegenerated in the phosphonic acid catalysis is about 9.76 wt. % of thereaction product mixture, the p-TsOH catalysis is about 6.92 wt. % ofthe reaction product mixture, and in the combined p-TsOH and phosphonicacid catalysis is about 18.53 wt. %. The combined acid catalysisgenerated about 2-3 times more of isosorbide when compared to the singleacid catalysis, while maintaining concomitantly a comparable level ofcompositional accountability for the respective reaction productmixtures of the three acid reactions. The product accountability of eachof the reactions ranged from 18.53% with H₃PO₃/p-TsOH; 6.92% withp-TsOH; 9.76% with H₃PO₃. All of the sorbitol is consumed in thecombined acid catalysis, while a significant percent remains unreactedfor both the H₃PO₃ (20.8%) and p-TsOH (17%) single acid catalysis. Allof the sorbitol is consumed in the combined acid catalysis, while asignificant percent remains unreacted for both the H₃PO₃ (20.8%) andp-TsOH (17%) single acid catalysis.

In FIG. 8, sorbitol is converted to isosorbide using 5 mol. % H₃PO₃, 0.1mol. % p-TsOH, 150° C., 1 h., in three reactions with each individualacid catalyst separately, and in combination. The amount of isosorbidegenerated in the phosphonic acid catalysis is about 5.18 wt. % of thereaction product mixture, the p-TsOH catalysis is about 7.13 wt. % ofthe reaction product mixture, and in the combined p-TsOH and phosphonicacid catalysis is about 14.12 wt. %. The combined acid catalysisgenerated about 2-3 times more of isosorbide when compared to the singleacid catalysis, while maintaining concomitantly a comparable level ofcompositional accountability for the respective reaction productmixtures of the three acid reactions. The product accountability of eachof the reactions ranged from 87.0% with H₃PO₃/p-TsOH; 91.7% with p-TsOH;94.1% with H₃PO₃. All of the sorbitol is consumed in the combined acidcatalysis, while a significant percent remains unreacted for both theH₃PO₃ (24.47 wt. %) and p-TsOH (13 wt. %) single acid catalysis. All ofthe sorbitol is consumed in the combined acid catalysis, while asignificant percent remains unreacted for both the H₃PO₃ (24.47%) andp-TsOH (13%) single acid catalysis.

In FIG. 9, sorbitol is converted to isosorbide using 2.5 mol. % H₃PO₃,0.1 mol. % p-TsOH, 140° C., 2 h., in three reactions with eachindividual acid catalyst separately, and in combination. The amount ofisosorbide generated in the phosphonic acid catalysis is about 5.18 wt.% of the reaction product mixture, the p-TsOH catalysis is about 7.13wt. % of the reaction product mixture, and in the combined p-TsOH andphosphonic acid catalysis is about 14.12 wt. %. The combined acidcatalysis generated about 2-3 times more of isosorbide when compared tothe single acid catalysis, while maintaining concomitantly a comparablelevel of compositional accountability for the respective reactionproduct mixtures of the three acid reactions. The product accountabilityof each of the reactions ranged from 87.0% with H₃PO3/p-TsOH; 91.7% withp-TsOH; 94.1% with H₃PO₃. All of the sorbitol is consumed in thecombined acid catalysis, while a significant percent remains unreactedfor both the H₃PO₃ (43.5 wt. %) and p-TsOH (17 wt. %) single acidcatalysis.

In FIG. 10, sorbitol is converted to isosorbide using 2.5 mol. % H₃PO₃,0.1 mol. % p-TsOH, 150° C., 1 h., in three reactions with eachindividual acid catalyst separately, and in combination. The amount ofisosorbide generated in the phosphonic acid catalysis is about 2.51 wt.% of the reaction product mixture, the p-TsOH catalysis is about 7.13wt. % of the reaction product mixture, and in the combined p-TsOH andphosphonic acid catalysis is about 20.16 wt. %. The combined acidcatalysis generated about 2-6 times more of isosorbide when compared tothe single acid catalysis, while maintaining concomitantly a comparablelevel of compositional accountability for the respective reactionproduct mixtures of the three acid reactions. The product accountabilityof each of the reactions ranged from 87.0% with H₃PO₃/p-TsOH; 91.7% withp-TsOH; 94.1% with H₃PO₃. All of the sorbitol is consumed in thecombined acid catalysis, while a significant percent remains unreactedfor both the H₃PO₃ (39.6 wt. %) and p-TsOH (13 wt. %) single acidcatalysis.

In FIG. 11, sorbitol is converted to isosorbide using 5 mol. % H₃PO₃,0.005 mol. % Ga(OTf)₃, 140° C., 2 h., in three reactions with eachindividual acid catalyst separately, and in combination. The amount ofisosorbide generated in the phosphonic acid catalysis is about 9.76 wt.% of the reaction product mixture, the Ga(OTf)₃ catalysis is 0 wt. % ofthe reaction product mixture, and in the combined Ga(OTf)₃ andphosphonic acid catalysis is about 11.62 wt. %. The combined acidcatalysis generated more of isosorbide when compared to the single acidcatalysis, while maintaining concomitantly a comparable level ofcompositional accountability for the respective reaction productmixtures of the three acid reactions. The product accountability of eachof the reactions ranged from 94.0% with H₃PO₃/Ga(OTf)₃; 99.9% withGa(OTf)₃; 89.7% with H₃PO₃.

In FIG. 12, sorbitol is converted to isosorbide using 5 mol. % H₃PO₃,0.005 mol. % Ga(OTf)₃, 130° C., 3 h., in three reactions with eachindividual acid catalyst separately, and in combination. The amount ofisosorbide generated in the phosphonic acid catalysis is about 2.91 wt.% of the reaction product mixture, the Ga(OTf)₃ catalysis is 0 wt. % ofthe reaction product mixture, and in the combined Ga(OTf)₃ andphosphonic acid catalysis is about 7.22 wt. %. The combined acidcatalysis generated more of isosorbide when compared to the single acidcatalysis, while maintaining concomitantly a comparable level ofcompositional accountability for the respective reaction productmixtures of the three acid reactions. The product accountability of eachof the reactions ranged from 95.1% with H₃PO₃/Ga(OTf)₃; 100% withGa(OTf)₃; 91.5% with H₃PO₃.

In FIG. 13, sorbitol is converted to isosorbide using 5 mol. % H₃PO₃,0.01 mol. % Ga(OTf)₃, 150° C., 1 h., in three reactions with eachindividual acid catalyst separately, and in combination. The amount ofisosorbide generated in the phosphonic acid catalysis is about 5.18 wt.% of the reaction product mixture, the Ga(OTf)₃ catalysis is about 0.63wt. % of the reaction product mixture, and in the combined Ga(OTf)₃ andphosphonic acid catalysis is about 15.09 wt. %. The combined acidcatalysis generated more of isosorbide when compared to the single acidcatalysis, while maintaining concomitantly a comparable level ofcompositional accountability for the respective reaction productmixtures of the three acid reactions. The product accountability of eachof the reactions ranged from 92.2% with H₃PO₃/Ga(OTf)₃; 98.4% withGa(OTf)₃; 94.1% with H₃PO₃.

In FIG. 14, sorbitol is converted to isosorbide using 5 mol. % H₃PO₃,0.01 mol. % Ga(OTf)₃, 140° C., 2 h., in three reactions with eachindividual acid catalyst separately, and in combination. The amount ofisosorbide generated in the phosphonic acid catalysis is about 9.76 wt.% of the reaction product mixture, the Ga(OTf)₃ catalysis is about 0.31wt. % of the reaction product mixture, and in the combined Ga(OTf)₃ andphosphonic acid catalysis is about 12.49 wt. %. The combined acidcatalysis generated more of isosorbide when compared to the single acidcatalysis, while maintaining concomitantly a comparable level ofcompositional accountability for the respective reaction productmixtures of the three acid reactions. The product accountability of eachof the reactions ranged from 92.2% with H₃PO₃/Ga(OTf)₃; 98.4% withGa(OTf)₃; 94.1% with H₃PO₃.

In FIG. 15, sorbitol is converted to isosorbide using 5 mol. % H₃PO₃,0.01 mol. % Ga(OTf)₃, 130° C., 3 h., in three reactions with eachindividual acid catalyst separately, and in combination. The amount ofisosorbide generated in the phosphonic acid catalysis is about 2.91 wt.% of the reaction product mixture, the Ga(OTf)₃ catalysis is 0.1 wt. %of the reaction product mixture, and in the combined Ga(OTf)₃ andphosphonic acid catalysis is about 8.76 wt. %. The combined acidcatalysis generated more of isosorbide when compared to the single acidcatalysis, while maintaining concomitantly a comparable level ofcompositional accountability for the respective reaction productmixtures of the three acid reactions. The product accountability of eachof the reactions ranged from 93.8% with H₃PO₃/Ga(OTf)₃; 99.8% withGa(OTf)₃; 91.5% with H₃PO₃.

In FIG. 16, sorbitol is converted to isosorbide using 5 mol. % H₃PO₃,0.05 mol. % Ga(OTf)₃, 140° C., 2 h., in three reactions with eachindividual acid catalyst separately, and in combination. The amount ofisosorbide generated in the phosphonic acid catalysis is about 9.76 wt.% of the reaction product mixture, the Ga(OTf)₃ catalysis is about 4.47wt. % of the reaction product mixture, and in the combined Ga(OTf)₃ andphosphonic acid catalysis is about 24.13 wt. %. The combined acidcatalysis generated more of isosorbide when compared to the single acidcatalysis, while maintaining concomitantly a comparable level ofcompositional accountability for the respective reaction productmixtures of the three acid reactions. The product accountability of eachof the reactions ranged from 89.6% with H₃PO₃/Ga(OTf)₃; 92.5% withGa(OTf)₃; 94.1% with H₃PO₃. All of the sorbitol is consumed in thecombined acid catalysis, while a significant percent remains unreactedfor both the H₃PO₃ (20.8 wt. %) and Ga(OTf)₃ (32.9 wt. %) single acidcatalysis.

In FIG. 17, sorbitol is converted to isosorbide using 5 mol. % H₃PO₃,0.05 mol. % Ga(OTf)₃, 150° C., 1 h., in three reactions with eachindividual acid catalyst separately, and in combination. The amount ofisosorbide generated in the phosphonic acid catalysis is about 5.18 wt.% of the reaction product mixture, the Ga(OTf)₃ catalysis is about 6.01wt. % of the reaction product mixture, and in the combined Ga(OTf)₃ andphosphonic acid catalysis is about 33.1 wt. %. The combined acidcatalysis generated about 5-6 times more of isosorbide when compared tothe single acid catalysis, while maintaining concomitantly a comparablelevel of compositional accountability for the respective reactionproduct mixtures of the three acid reactions. The product accountabilityof each of the reactions ranged from 83.9% with H₃PO₃/GA(OTf)₃; 87.6%with Ga(OTf)₃; 94.1% with H₃PO₃. All of the sorbitol is consumed in thecombined acid catalysis, while a significant percent remains unreactedfor both the H₃PO₃ (24.5 wt. %) and Ga(OTf)₃ (28.9 wt. %) single acidcatalysis.

In FIG. 18, sorbitol is converted to isosorbide using 5 mol. % H₃PO₃,0.1 mol. % Al(OTf)₃, 150° C., 1 h., in three reactions with eachindividual acid catalyst separately, and in combination. The amount ofisosorbide generated in the phosphonic acid catalysis is about 5.18 wt.% of the reaction product mixture, the Al(OTf)₃ catalysis is about 13.39wt. % of the reaction product mixture, and in the combined Al(OTf)₃ andphosphonic acid catalysis is about 40.07 wt. %. The combined acidcatalysis generated about 5-6 times more of isosorbide when compared tothe single acid catalysis, while maintaining concomitantly a comparablelevel of compositional accountability for the respective reactionproduct mixtures of the three acid reactions. The product accountabilityof each of the reactions ranged from 85.8% with H₃PO₃/Al(OTf)₀₃; 89.0%with Al(OTf)₃; 94.1% with H₃PO₃. All of the sorbitol is consumed in thecombined acid catalysis, while a significant percent remains unreactedfor both the H₃PO₃ (24.5 wt. %) and Al(OTf)₃ (9.8 wt. %) single acidcatalysis.

In FIG. 19, sorbitol is converted to isosorbide using 5 mol. % H₃PO₃,0.01 mol. % Bi(OTf)₃, 0.05 mol. % p-TsOH, 150° C., 1 h., in fourreactions with each individual acid catalyst separately, and incombination. The amount of isosorbide generated in the phosphonic acidcatalysis is about 5.18 wt. % of the reaction product mixture, theBi(OTf)₃ catalysis is 0 wt. % of the reaction product mixture, thep-TsOH catalysis is 2.36 wt. % of the reaction product mixture, and inthe combined Bi(OTf)₃, p-TsOH and phosphonic acid catalysis is about19.63 wt. %. The combined acid catalysis generated about 5-6 times moreof isosorbide when compared to the single acid catalysis, whilemaintaining concomitantly a comparable level of compositionalaccountability for the respective reaction product mixtures of the threeacid reactions. The product accountability of each of the reactionsranged from 87.1% with H₃PO₃/Bi(OTf)₃/p-TsOH; 98.4% with Bi(OTf)₃; 93.7%p-TsOH; 94.1% with H₃PO₃. All of the sorbitol is consumed in thecombined acid catalysis, while a significant percent remains unreactedfor both the H₃PO₃ (24.47 wt. %), Bi(OTf)₃ (74.6 wt. %), and p-TsOH(37.8 wt. %) single acid catalysis.

In FIG. 20, sorbitol is converted to isosorbide using 2.5 mol. % H₃PO₃,0.01 mol. % Bi(OTf)₃, 0.1 mol. % p-TsOH, 150° C., 1 h., in fourreactions with each individual acid catalyst separately, and incombination. The amount of isosorbide generated in the phosphonic acidcatalysis is about 2.51 wt. % of the reaction product mixture, theBi(OTf)₃ catalysis is 0 wt. % of the reaction product mixture, thep-TsOH catalysis is 7.13 wt. % of the reaction product mixture, and inthe combined Bi(OTf)₃, p-TsOH and phosphonic acid catalysis is about39.07 wt. %. The combined acid catalysis generated about 5-10 times moreof isosorbide when compared to the single acid catalysis, whilemaintaining concomitantly a comparable level of compositionalaccountability for the respective reaction product mixtures of the threeacid reactions. The product accountability of each of the reactionsranged from 88.5% with H₃PO₃/Bi(OTf)₃/p-TsOH; 98.4% with Bi(OTf)₃; 91.7%with p-TsOH; 95.4% with H₃PO₃. All of the sorbitol is consumed in thecombined multi-acid catalysis, while a significant percent remainsunreacted for both the H₃PO₃ (39.6 wt. %), Bi(OTf)₃ (74.6 wt. %), andp-TsOH (13 wt. %) single acid catalysis.

In FIG. 21, sorbitol is converted to isosorbide using 5 mol. % H₃PO₃,0.01 mol. % Hf(OTf)₄, 0.05 mol. % p-TsOH, 150° C., 1 h., in fourreactions with each individual acid catalyst separately, and incombination. The amount of isosorbide generated in the phosphonic acidcatalysis is about 5.18 wt. % of the reaction product mixture, theHf(OTf)₄ catalysis is about 6.62 wt. % of the reaction product mixture,the p-TsOH catalysis is 2.36 wt. % of the reaction product mixture, andin the combined Hf(OTf)₄, p-TsOH and phosphonic acid catalysis is about29.18 wt. %. The combined acid catalysis generated about 5-10 times moreof isosorbide when compared to the single acid catalysis, whilemaintaining concomitantly a comparable level of compositionalaccountability for the respective reaction product mixtures of the threeacid reactions. The product accountability of each of the reactionsranged from 86.3% with H₃PO₃/Bi(OTf)₃/p-TsOH; 96.6% with Hf(OTf)₄, 93.7%with p-TsOH; 94.1% with H₃PO₃. All of the sorbitol is consumed in thecombined multi-acid catalysis, while a significant percent remainsunreacted for both the H₃PO₃ (24.47 wt. %), Hf(OTf)₄ (47.4 wt. %), andp-TsOH (37.81 wt. %) single acid catalysis.

For comparison, Table 4 summarizes the catalysis results for dehydrativecyclization of sorbitol to isosorbide using sulfuric acid alone.

TABLE 4 H₂SO₄ Load Iso- 1,4- 2,5- Account- (mol Time Temp Sorbitolsorbide sorbitan sorbitan(s) ability %) (min) (° C.) (wt. %) (wt. %)(wt. %) (wt. %) (%) 0.1 180 130 16 5.91 63.20 6.29 91.40 0.1 120 140 021.74 49.28 12.31 83.33 0.1 60 150 0 23.82 47.95 10.87 82.64 0.5 180 1300 34.26 37.44 9.35 81.05 0.5 120 140 0 69.90 0.00 9.75 79.65 0.5 60 1500 69.58 0.00 8.26 77.84 1 180 130 0 61.23 11.23 8.04 80.50 1 120 140 069.67 0.00 7.77 77.44 1 60 150 0 67.82 2.21 3.59 73.62

For comparison, Table 5 summarizes the catalysis results for dehydrativecyclization of sorbitol to isosorbide using phosphonic acid alone.

TABLE 5 H₃PO₃ Load Iso- 1,4- 2,5- Account- (mol Time Temp Sorbitalsorbide sorbitan sorbitan(s) ability %) (min) (° C.) (wt. %) (wt. %)(wt. %) (wt. %) (%) 5 180 130 33.16 2.91 42.61 12.81 91.49 5 60 15024.47 5.18 49.00 15.40 94.05 5 120 160 0 35.32 35.73 17.71 88.76 10 120140 0 12.30 58.24 17.93 88.47 10 60 150 0 16.33 57.50 15.37 89.20 2.5 60150 39.65 2.51 41.68 11.57 95.41 2.5 120 140 43.52 2.23 40.28 10.6896.71 2.5 120 170 0 25.92 46.83 16.53 89.28

For comparison, Table 6 summarizes the catalysis results for dehydrativecyclization of sorbitol to isosorbide using p-toluenesulfonic acidalone.

TABLE 6 p-TsOH Load Iso- 1,4- 2,5- Account- (mol Time Temp Sorbitolsorbide sorbitan sorbitan(s) ability %) (min) (° C.) (wt. %) (wt. %)(wt. %) (wt. %) (%) 0.1 180 130 32.23 2.68 51.32 9.14 95.37 0.1 120 14017.05 6.92 63.22 6.22 93.41 0.1 60 150 22.62 7.13 59.24 2.69 91.68 0.5180 130 0 26.65 50.32 10.59 87.56 0.5 120 140 0 35.51 37.75 10.04 83.300.5 60 150 0 42.20 28.29 11.06 81.55

For comparison, Table 7 summarizes the catalysis results for dehydrativecyclization of sorbitol to isosorbide using galliumtrifluoromethanesulfonate alone.

TABLE 7 Ga(OTf)₃ Load Iso- 1,4- 2,5- Account- (mol Time Temp Sorbitolsorbide sorbitan sorbitan(s) ability %) (min) (° C.) (wt. %) (wt. %)(wt. %) (wt. %) (%) 0.005 180 130 89.2 0 10.62 1.92 100.00 0.005 120 14078.5 0.00 25.16 3.77 99.87 0.005 60 150 82.2 0.00 14.69 3.17 100.00 0.01180 130 81.8 0.00 14.72 2.90 99.82 0.01 120 140 73.7 0.31 26.01 2.9799.23 0.01 60 150 67.0 0.63 24.79 6.02 98.38 0.05 120 140 32.9 4.4747.02 8.08 92.51 0.05 60 150 28.9 6.01 44.13 8.53 87.62

The present invention has been described in general and in detail by wayof examples. Persons of skill in the art understand that the inventionis not limited necessarily to the embodiments specifically disclosed,but that modifications and variations may be made without departing fromthe scope of the invention as defined by the following claims or theirequivalents, including other equivalent components presently know or tobe developed, which may be used within the scope of the invention.Therefore, unless changes otherwise depart from the scope of theinvention, the changes should be construed as being included herein.

We claim:
 1. A process for preparing a cyclic dehydration productcomprising: contacting a sugar alcohol with a mixed-acid catalystreaction mixture containing a reducing Brønsted acid, having a pKa ofabout 1.0-1.5, in combination with at least a strong Brønsted acid or aLewis acid, having a pKa≦0, or both kinds of acids at a temperature fora sufficient time to dehydrate and ring close said sugar alcohol to acorresponding cyclic dehydration product of the sugar alcohol in aproduct mixture.
 2. The process according to claim 1, wherein saidproduct mixture has at least a 3% increase in yield of said cyclicdehydration product relative to a dehydration reaction using either saidreducing Brønsted acid, said strong Brønsted acid, or Lewis acidseparately and alone under the same respective catalyst load for thesame reaction time and temperature.
 3. The process according to claim 1,wherein said product mixture has at least a 5% increase in relativeyield of said cyclic dehydration product relative to a dehydrationreaction using either said reducing Brønsted acid, said strong Brønstedacid, or Lewis acid separately and alone under the same respectivecatalysts load for the same reaction time and temperature.
 4. Theprocess according to claim 1, wherein said product mixture has arelative percentage of compositional accountability that is either a)equal to, b) greater than or c) not less than about 20% of acompositional accountability for a product mixture prepared from adehydration reaction using either said reducing Brønsted acid, saidstrong Brønsted acid, or Lewis acid separately and alone under the samerespective catalyst load for the same reaction time and temperature. 5.The process according to claim 1, wherein said sugar alcohol is at leastone of: sorbitol, mannitol, iditol, xylitol, erythritol, and1,2,5,6-hexanetetrol (HTO).
 6. The process according to claim 1, whereinsaid reducing Brønsted acid is phosphonic acid (H₃PO₃).
 7. The processaccording to claim 1, wherein said strong Brønsted acid is selected fromthe group consisting of: hydrochloric acid (HCl), sulfuric acid (H₂SO₄),p-toluenesulfonic acid, methane sulfonic acid, andtrifluoromethansulfonic acid.
 8. The process according to claim 1,wherein said Lewis acid is selected from the group consisting of:aluminum trifluoromethanesulfonate (Al(OTf)₃), galliumtrifluoromethanesulfonate (Ga(OTf)₃, bismuth trifluormethanesulfonate(Bi (OTf)₃), scandium trifluoromethanesulfonate (Sc(OTf)₃), indiumtrifluoromethanesulfonate (In(OTf)₃), tin triflate (Sn(OTf)₂), andhafnium triflate (Hf(OTf)₄).
 9. The process according to claim 1,wherein a ratio of said reducing Brønsted acid to said Brønsted acid orLewis acid alone or in combination is from about 1000:1 to about 5:1.10. The process according to claim 1, wherein said temperature is about120° C. to about 190° C.
 11. The process according to claim 10, whereinsaid temperature is between about 125° C. and about 165° C.
 12. Theprocess according to claim 1, wherein said reducing Brønsted acid ispresent at a concentration of about 1.0 mol. % to about 20 mol. %relative to the sugar alcohol.
 13. The process according to claim 1,wherein said Brønsted acid is present at a concentration of about 0.01mol. % to about 2.0 mol. % relative to the sugar alcohol.
 14. Theprocess according to claim 1, wherein said Lewis acid is present at aconcentration of about 0.005 mol. % to about 0.5 mol. % relative to thesugar alcohol.
 15. The process according to claim 1, wherein when saidsugar alcohol is sorbitol, said product mixture has at least a 2×increase in relative yield of isosorbide relative to a dehydrationreaction using either said reducing Brønsted acid, said strong Brønstedacid, or Lewis acid separately and alone under the same respectivecatalysts load for the same reaction time and temperature.
 16. Amixed-acid catalyst dehydration process comprising: contacting a sugaralcohol with phosphonic acid (H₃PO₃) and at least a strong Brønsted acidor Lewis acid, having a pKa≦0, in a solution at a temperature and for atime to dehydrate said sugar alcohol, wherein a ratio of said phosphonicacid and either said strong Brønsted acid or Lewis acid alone or incombination is from about 1000:1 to about 5:1, and producing at least a3% increase in relative yield of cyclic dehydration products, and arelative percentage of compositional accountability that is a) equal to,b) greater than or c) not less than about 20% that of an compositionalaccountability relative to a dehydration reaction using either saidphosphonic acid, said strong Brønsted acid, or Lewis acid separately andalone under the same respective acid catalyst load for the same reactiontime and temperature.
 17. The process according to claim 16, whereinsaid sugar alcohol is at least one of: sorbitol, mannitol, and iditol.18. The process according to claim 16, wherein said strong Brønsted acidis selected from the group consisting of: hydrochloric acid (HCl),sulfuric acid (H₂SO₄), p-toluenesulfonic acid, methane sulfonic acid,and trifluoromethansulfonic acid.
 19. The process according to claim 16,wherein said Lewis acid is selected from the group consisting ofaluminum trifluoromethanesulfonate (Al(OTf)₃), galliumtrifluoromethanesulfonate (Ga(OTf)₃, bismuth trifluormethanesulfonate(Bi (OTf)₃), scandium trifluoromethanesulfonate (Sc(OTf)₃), indiumtrifluoromethanesulfonate (In(OTf)₃), tin triflate (Sn(OTf)₂), andhafnium triflate (Hf(OTf)₄).
 20. The process according to claim 16,wherein said reducing Brønsted acid is present at a concentration ofabout 1.0 mol. % to about 20 mol. % relative to said sugar alcohol. 21.The process according to claim 16, wherein said strong Brønsted acid ispresent at a concentration of about 0.01 mol. % to about 2.0 mol. %relative to said sugar alcohol.
 22. The process according to claim 16,wherein said Lewis acid is present at a concentration of about 0.005mol. % to about 0.5 mol. % relative to said sugar alcohol.